It has been well established that both genetic background and the environment can have pronounced effects on how mice respond to drugs of abuse, including both psychostimulants and the opiates. In particular, different strains of mice respond differentially to drug treatment, and acut7e sleep deprivation alters the response to a number of drugs of abuse. However, essentially nothing is known about how the genetic background affects the response to drugs of abuse in animals with disrupted sleep. Examining the effects of sleep disruption on the response to drugs of abuse in mice with different genetic backgrounds is particularly important since one of the hallmarks of substance abuse in humans is disrupted sleep. Poor sleep, whether due to genetic or environmental causes, may in itself predispose one to abuse and drug addiction. One of the overall objectives of the proposed studies is to determine if the effects of acute sleep deprivation on the response to drugs of abuse in mice is dependent on genetic background. Since very little is known about the effects of chronic sleep loss on the response to drugs of abuse, a second overall objective will address this question and determine if the genetic background influences the effects of chronic partial sleep deprivation on the response to drugs of abuse. Six different strains of mice will be used to test hypotheses. that genetic differences in either sensitivity or sensitization of the locomotor response to either cocaine or morphine are affected by either acute or chronic partial sleep deprivation. The completion of the proposed studies is expected to not only lead to a better understanding of how genetic differences predispose mice to be more or less responsive to cocaine and/or morphine under both baseline and sleep deprivation conditions, but also will provide new insights for optimizing the genetic animal models to be used for ultimately elucidating the genetic, neurochemical and biochemical mechanisms underlying the actions of drugs of abuse. The use of these genetic animal models is expected to lead to new genetic and pharmacological strategies for the treatment of drug abuse and addiction.